Description of a novel subtype of acute myeloid leukemia defined by recurrent <i>CBFB</i> insertions
Authors: Georgina L. Ryland, Masayuki Umeda, Linda Holmfeldt, Sören Lehmann, Morten Krogh Herlin, Jing Ma, Mahsa Khanlari, Jeffrey E. Rubnitz, Rhonda E. Ries, Hansen J. Kosasih, Paul G. Ekert, Hwee Ngee Goh, Ing S. Tiong, Sean M. Grimmond, Claudia Haferlach, Ryan B. Day, Timothy J. Ley, Soheil Meshinchi, Xiaotu Ma, Piers Blombery, Jeffery M. Klco
Journal: Blood (2022)

Letter to Blood| February 16, 2023 Description of a novel subtype of acute myeloid leukemia defined by recurrent CBFB insertions Georgina L. Ryland, Georgina L. Ryland ∗ Department of Pathology, Peter MacCallum Cancer Centre, Melbourne, VIC, AustraliaCentre for Cancer Research, University of Melbourne, Parkville, VIC, AustraliaSir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC, Australia https://orcid.org/0000-0002-4990-0961 Search for other works by this author on: This Site PubMed Google Scholar Masayuki Umeda, Masayuki Umeda ∗ Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN Search for other works by this author on: This Site PubMed Google Scholar Linda Holmfeldt, Linda Holmfeldt Department of Immunology, Genetics, and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, SwedenThe Beijer Laboratory, Uppsala, Sweden https://orcid.org/0000-0003-4140-3423 Search for other works by this author on: This Site PubMed Google Scholar Sören Lehmann, Sören Lehmann Department of Hematology, Karolinska University Hospital, Stockholm, Sweden Search for other works by this author on: This Site PubMed Google Scholar Morten Krogh Herlin, Morten Krogh Herlin Department of Clinical Genetics, Aarhus University Hospital, Aarhus, DenmarkDepartment of Pediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark https://orcid.org/0000-0001-7179-4643 Search for other works by this author on: This Site PubMed Google Scholar Jing Ma, Jing Ma Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN Search for other works by this author on: This Site PubMed Google Scholar Mahsa Khanlari, Mahsa Khanlari Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN Search for other works by this author on: This Site PubMed Google Scholar Jeffrey E. Rubnitz, Jeffrey E. Rubnitz Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN https://orcid.org/0000-0001-9885-3527 Search for other works by this author on: This Site PubMed Google Scholar Rhonda E. Ries, Rhonda E. Ries Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA Search for other works by this author on: This Site PubMed Google Scholar Hansen J. Kosasih, Hansen J. Kosasih Murdoch Children's Research Institute, Parkville, VIC, Australia https://orcid.org/0000-0002-0428-6195 Search for other works by this author on: This Site PubMed Google Scholar Paul G. Ekert, Paul G. Ekert Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC, AustraliaMurdoch Children's Research Institute, Parkville, VIC, AustraliaChildren's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Sydney, NSW, AustraliaCancer Immunology Program, Peter MacCallum Cancer Centre, Parkville, VIC, AustraliaDiscipline of Paediatrics and Child Health, School of Clinical Medicine, UNSW Medicine & Health, UNSW Sydney, Sydney, NSW, Australia Search for other works by this author on: This Site PubMed Google Scholar Hwee Ngee Goh, Hwee Ngee Goh Department of Pathology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia Search for other works by this author on: This Site PubMed Google Scholar Ing S. Tiong, Ing S. Tiong Department of Pathology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia https://orcid.org/0000-0001-7417-4343 Search for other works by this author on: This Site PubMed Google Scholar Sean M. Grimmond, Sean M. Grimmond Centre for Cancer Research, University of Melbourne, Parkville, VIC, Australia https://orcid.org/0000-0002-8102-7998 Search for other works by this author on: This Site PubMed Google Scholar Claudia Haferlach, Claudia Haferlach Munich Leukemia Laboratory, Munich, Germany Search for other works by this author on: This Site PubMed Google Scholar Ryan B. Day, Ryan B. Day Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO https://orcid.org/0000-0002-4376-4663 Search for other works by this author on: This Site PubMed Google Scholar Timothy J. Ley, Timothy J. Ley Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO https://orcid.org/0000-0002-9913-0520 Search for other works by this author on: This Site PubMed Google Scholar Soheil Meshinchi, Soheil Meshinchi Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA Search for other works by this author on: This Site PubMed Google Scholar Xiaotu Ma, Xiaotu Ma Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN Search for other works by this author on: This Site PubMed Google Scholar Piers Blombery, Piers Blombery † Department of Pathology, Peter MacCallum Cancer Centre, Melbourne, VIC, AustraliaSir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC, AustraliaClinical Haematology, Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, VIC, Australia Search for other works by this author on: This Site PubMed Google Scholar Jeffery M. Klco Jeffery M. Klco † Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN Search for other works by this author on: This Site PubMed Google Scholar Blood (2023) 141 (7): 800–805. https://doi.org/10.1182/blood.2022017874 Article history Submitted: July 21, 2022 Accepted: September 16, 2022 Share Icon Share Facebook Twitter LinkedIn MailTo Tools Icon Tools Request Permissions Cite Icon Cite Search Site Citation Georgina L. Ryland, Masayuki Umeda, Linda Holmfeldt, Sören Lehmann, Morten Krogh Herlin, Jing Ma, Mahsa Khanlari, Jeffrey E. Rubnitz, Rhonda E. Ries, Hansen J. Kosasih, Paul G. Ekert, Hwee Ngee Goh, Ing S. Tiong, Sean M. Grimmond, Claudia Haferlach, Ryan B. Day, Timothy J. Ley, Soheil Meshinchi, Xiaotu Ma, Piers Blombery, Jeffery M. Klco; Description of a novel subtype of acute myeloid leukemia defined by recurrent CBFB insertions. Blood 2023; 141 (7): 800–805. doi: https://doi.org/10.1182/blood.2022017874 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBlood Search Subjects: Free Research Articles, Myeloid Neoplasia TO THE EDITOR: Molecular analysis of pediatric and adult acute myeloid leukemia (AML) is used routinely to identify subtype-defining driver structural variants and mutations which may provide important information for risk stratification. For example, the core-binding factor (CBF) AML subgroup defined by t(8;21) RUNX1::RUNX1T1 or inv(16)/t(16;16) CBFB::MYH11 are associated with favorable outcomes.1,2 Despite the extensive genomic characterization of pediatric and adult AML, there remains an important proportion of previously unclassified cases where new driver lesions are still being identified, including those that can influence patient management owing to their association with outcomes. This includes the recent identification of tandem duplications in UBTF in pediatric AML3,4 and structural variants that dysregulate BCL11B in lineage-ambiguous acute leukemia.5 Herein we describe an additional new subtype of AML characterized by a recurrent insertion mutation in CBFB. We... References 1.Byrd JC, Mrózek K, Dodge RK, et al. Pretreatment cytogenetic abnormalities are predictive of induction success, cumulative incidence of relapse, and overall survival in adult patients with de novo acute myeloid leukemia: results from Cancer and Leukemia Group B (CALGB 8461). Blood. 2002;100(13):4325-4336.Google ScholarCrossrefSearch ADS PubMed 2.Schlenk RF, Benner A, Krauter J, et al. Individual patient data-based meta-analysis of patients aged 16 to 60 years with core binding factor acute myeloid leukemia: a survey of the German Acute Myeloid Leukemia Intergroup. J Clin Oncol. 2004;22(18):3741-3750.Google ScholarCrossrefSearch ADS 3.Umeda M, Ma J, Huang BJ, et al. Integrated genomic analysis identifies UBTF tandem duplications as a recurrent lesion in pediatric acute myeloid leukemia. Blood Cancer Discov. 2022;3(3):194-207.Google ScholarCrossrefSearch ADS PubMed 4.Stratmann S, Yones SA, Mayrhofer M, et al. Genomic characterization of relapsed acute myeloid leukemia reveals novel putative therapeutic targets. Blood Adv. 2021;5(3):900-912.Google ScholarCrossrefSearch ADS PubMed 5.Montefiori LE, Bendig S, Gu Z, et al. Enhancer hijacking drives oncogenic BCL11B expression in lineage-ambiguous stem cell leukemia. Cancer Discov. 2021;11(11):2846-2867.Google ScholarCrossrefSearch ADS PubMed 6.de Bruijn M.F.T.R., Speck NA. Core-binding factors in hematopoiesis and immune function. Oncogene. 2004;23(24):4238-4248.Google ScholarPubMed 7.Faber ZJ, Chen X, Gedman AL, et al. The genomic landscape of core-binding factor acute myeloid leukemias. Nat Genet. 2016;48(12):1551-1556.Google ScholarPubMed 8.Walter K, Cockerill PN, Barlow R, et al. Aberrant expression of CD19 in AML with t(8;21) involves a poised chromatin structure and PAX5. Oncogene. 2010;29(20):2927-2937.Google ScholarPubMed 9.Bolouri H, Farrar JE, Triche T, et al. The molecular landscape of pediatric acute myeloid leukemia reveals recurrent structural alterations and age-specific mutational interactions. Nat Med. 2018;24(1):103-112.Google ScholarPubMed 10.Ma X, Liu Y, Liu Y, et al. Pan-cancer genome and transcriptome analyses of 1,699 paediatric leukaemias and solid tumours. Nature. 2018;555(7696):371-376.Google ScholarPubMed 11.Alexander TB, Gu Z, Iacobucci I, et al. The genetic basis and cell of origin of mixed phenotype acute leukaemia. Nature. 2018;562(7727):373-379.Google ScholarCrossrefSearch ADS PubMed 12.Fornerod M, Ma J, Noort S, et al. Integrative genomic analysis of pediatric myeloid-related acute leukemias identifies novel subtypes and prognostic indicators. Blood Cancer Discov. 2021;2(6):586-599.Google ScholarCrossrefSearch ADS PubMed 13.Stratmann S, Yones SA, Garbulowski M, et al. Transcriptomic analysis reveals proinflammatory signatures associated with acute myeloid leukemia progression. Blood Adv. 2022;6(1):152-164.Google ScholarCrossrefSearch ADS PubMed 14.Petti AA, Khan SM, Xu Z, et al. Genetic and transcriptional contributions to relapse in normal karyotype acute myeloid leukemia. Blood Cancer Discov. 2022;3(1):32-49.Google ScholarCrossrefSearch ADS PubMed © 2023 by The American Society of Hematology2023 © 2023 by The American Society of Hematology2023 You do not currently have access to this content. Sign in via your Institution